Effect of systemic high dose vitamin C therapy on forearm blood flow reactivity during endotoxemia in healthy human subjects

Vascul Pharmacol. 2014 Apr;61(1):25-9. doi: 10.1016/j.vph.2014.01.007. Epub 2014 Feb 8.

Abstract

Objective: Acute inflammation induced by administration of Escherichia coli lipopolysaccharide endotoxin (LPS) reduces plasma concentrations of vitamin C and impairs vascular endothelium-derived nitric oxide (NO) bioactivity. We tested the hypothesis that systemically administered high dose vitamin C restores the endogenous anti-oxidant potential and improves NO-dependent vasodilatation in the forearm vasculature.

Design & setting: 36 male subjects were enrolled in this balanced, placebo controlled cross-over study. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glyceryl-trinitrate (GTN), a sensitive test for endothelial function, was assessed at baseline and 4h after LPS-administration (20 IU/kg i.v). The effect of two different doses of intravenous vitamin C (Vitamin C-Injektopas®), 320 mg/kg and 480 mg/kg over 2h, or placebo on forearm vascular function was studied after LPS.

Main results: LPS caused transient flu-like symptoms, decreased plasma vitamin C concentrations and reduced the ACh-dependent increase in FBF by up to 76%. Vitamin C at a mean plasma concentration of 3.2 or 4.9 mmol/L restored the response to ACh compared to baseline.

Conclusion: High dose systemic vitamin C recovers LPS-induced endothelium-dependent vasodilation in the forearm resistance vasculature. This provides a rationale for a further clinical study of the systemic vitamin C effect under inflammatory conditions.

Keywords: Endothelial dysfunction; Endotoxemia; Forearm blood flow; Inflammation; Vitamin C.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ascorbic Acid / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Endotoxemia / drug therapy*
  • Endotoxemia / physiopathology
  • Forearm / blood supply*
  • Healthy Volunteers
  • Humans
  • Lipopolysaccharides / pharmacology
  • Male
  • Regional Blood Flow / drug effects

Substances

  • Lipopolysaccharides
  • Ascorbic Acid